Scars form in response to cutaneous injury as part of the natural wound healing process. Wound healing is a lengthy and continuous process, although it is typically recognized as occurring in stages. The process begins immediately after injury, with an inflammatory stage. During this stage, which typically lasts from two days to one week (depending on the wound), damaged tissues and foreign matter are removed from the wound. The proliferative stage occurs at a time after the inflammatory stage and is characterized by fibroblast proliferation and collagen and proteoglycan production. It is during the proliferative stage that the extracellular matrix is synthesized in order to provide structural integrity to the wound. The proliferative stage usually lasts about four days to several weeks, depending on the nature of the wound, and it is during this stage when hypertrophic scars usually form. The last stage is called the remodeling stage. During the remodeling stage the previously constructed and randomly organized matrix is remodeled into an organized structure that is highly cross-linked and aligned to increase mechanical strength.
The ability to repair the human body without scarring has been a goal of the medicine for many years. Human tissue banks and synthetic polymers are not currently meeting the need for repair or replacement of body parts, and thus there is a large market for advanced tissue engineering products, both synthetic and biologicals. However, tissue engineered skin substitutes provide only limited success in replacing skin. Synthetic polymers, plastics, and surface-coated metals may have different degrees of immunogenicity and suffer from significant limitations that prohibit their broad applications. A major limitation is that cells cannot remodel them after implantation. They are highly susceptible to microbial infection, and some undergo calcification. Furthermore, synthetic vascular conduits have a high incidence of occlusion after peripheral vascular bypass procedures.
Tissue engineering of skin requires biomaterial techniques capable of recapitulating both cellular and non-cellular elements. An important non-cellular element that plays a critical role in regulating skin behavior is the dermal extracellular matrix (ECM). This complex environment not only houses the myriad cell types involved in skin homeostasis and repair, but also provides mechanical stability, enables metabolite and cellular movement, and is constantly remodeled in response to local and systemic cues. Dermal scaffolds, derived from both native and synthetic sources, constitute the foundation for skin replacement techniques and have been used with variable success. Native dermal sources, such as decellularized cadaveric skin, are limited by cost, donor availability, and disease transmission concerns.
Current skin substitutes comprise of primitive animal collagen scaffolds that provide a conduit for tissue ingrowth. The success of these scaffolds has been limited due to poor incorporation by the host tissue, resulting in the formation of scar tissue rather than regenerated skin. In addition to poor tissue ingrowth, these products are plagued by infection, chronic inflammation, allergic reaction, excessive redness, pain, swelling, or blistering. Therefore, there is an urgent need for more complex skin substitutes that are nontoxic, biodegradable, and closely resemble a regenerative environment.
Improved skin substitutes for preventing or ameliorating the formation of scars and improving healing are therefore desirable for many clinical purposes.